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• W2784850923 abstract "We have concerns about the assertion of Philipp Schuetz and colleagues1Schuetz P Wirz Y Sager R et al.Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis.Lancet Infect Dis. 2018; 18: 95-107Summary Full Text Full Text PDF PubMed Scopus (253) Google Scholar that treatment of lower respiratory tract infections with procalcitonin-guided antibiotics reduces mortality. We pose three issues, formed on the basis of further research of the data online.2openMetaAnalysis ContributorsLower respiratory tract infection treatment guided by procalcitonin.http://openmetaanalysis.github.io/lrti-pct/Google Scholar First, we are concerned about the accuracy of representation of patients with lower respiratory tract infections by studies that show the benefit of antibiotic therapy. The forest plot shows no advantage of antibiotic intervention on lower respiratory tract infections among the emergency department trials, in which almost all patients had lower respiratory tract infections; whereas, studies done in intensive care units show a stronger and more substantial effect of this treatment on the infections.1Schuetz P Wirz Y Sager R et al.Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis.Lancet Infect Dis. 2018; 18: 95-107Summary Full Text Full Text PDF PubMed Scopus (253) Google Scholar However, we calculated that the median prevalence of lower respiratory tract infections in intensive care unit trials was 46% (IQR 35–64), with some trials having less than 5% of patients with lower respiratory tract infections.1Schuetz P Wirz Y Sager R et al.Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis.Lancet Infect Dis. 2018; 18: 95-107Summary Full Text Full Text PDF PubMed Scopus (253) Google Scholar Second, no dose–response effect of circulating procalcitonin testing on mortality reduction exists. The full Cochrane report shows that benefit was confined to studies with low adherence to the procalcitonin protocols.3Schuetz P Wirz Y Sager R et al.Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections.Cochrane Database Syst Rev. 2017; 10 (CD007498.)PubMed Google Scholar Our meta-regression of mortality reduction by rate of adherence shows an inverse association that is borderline significant; thus, an increased adherence to the protocol decreases the benefit to the patient. Investigation of this association could be improved if the authors add the adherence rate as an additional cofactor to the multivariable hierarchical regression. If the adherence rate is a significant, inverse cofactor, then the role of procalcitonin testing, or at least the design of the procalcitonin protocols, needs further reconsideration. Finally, optimisation of care might be inconsistent in the control groups. The one study that showed significant benefit from procalcitonin testing does not describe guidance or an organised approach for usual care.4de Jong E, van Oers JA, Beishuizen A, et al. Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial. Lancet Infect Dis; 16: 819–27.Google Scholar This bias was described in a randomised controlled trial of extracorporeal membrane oxygenation (ECMO).5Morris AH Wallace CJ Menlove RL et al.Randomized clinical trial of pressure-controlled inverse ratio ventilation and extracorporeal CO2 removal for adult respiratory distress syndrome.Am J Respir Crit Care Med. 1994; 149: 295-305Crossref PubMed Scopus (754) Google Scholar The trial showed no advantage from ECMO although the survival of patients treated with this therapy was similar to previous studies. However, the authors had protocolised the care in the control group and found higher than expected survival, which negated the results of ECMO.6East TD Heermann LK Bradshaw RL et al.Efficacy of computerized decision support for mechanical ventilation: results of a prospective multi-center randomized trial.Proc AMIA Symp. 1999; : 251-255PubMed Google Scholar Similarly, comparison of an intervention such as procalcitonin testing with usual care rather than optimal care is arguably unethical.7Djulbegovic B Lacevic M Cantor A et al.The uncertainty principle and industry-sponsored research.Lancet. 2000; 356: 635-638Summary Full Text Full Text PDF PubMed Scopus (406) Google Scholar These matters could similarly affect the interpretation of reduced exposure to antibiotics from procalcitonin testing among patients with lower respiratory tract infections. We encourage exploration of antibiotic exposure duration, and the degree of adherence to protocols in the control groups. We declare no competing interests. Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysisUse of procalcitonin to guide antibiotic treatment in patients with acute respiratory infections reduces antibiotic exposure and side-effects, and improves survival. Widespread implementation of procalcitonin protocols in patients with acute respiratory infections thus has the potential to improve antibiotic management with positive effects on clinical outcomes and on the current threat of increasing antibiotic multiresistance. Full-Text PDF Reassessment of a meta-analysis of procalcitonin-guided antibiotic therapy for lower respiratory tract infectionsIn their meta-analysis, Phillip Schuetz and colleagues1 found a clinically significant, 30-day mortality benefit of procalcitonin-directed treatment in patients with acute respiratory infections across all treatment settings. The meta-analysis was valid and reproducible, with nearly identical control and treatment groups and attention to allocation concealment, and masked outcome assessment of the source randomised controlled trials. Full-Text PDF Reassessment of a meta-analysis of procalcitonin-guided antibiotic therapy for lower respiratory tract infections – Authors' replyWe agree with Neil Gaskill that based on our analysis, the largest effects of procalcitonin protocols on antibiotic consumption were found in patients in primary care and the emergency department, with reductions in antibiotic use of around 65% and 35%, respectively.1 However, the effects of procalcitonin-guided antibiotic treatment on mortality were most pronounced in critically-ill patients at highest risk for fatal outcome. We did not find evidence for interaction by setting or respiratory infection, suggesting that procalcitonin-guided care has similar effects among the subgroups. Full-Text PDF" @default.
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• W2784850923 title "Reassessment of a meta-analysis of procalcitonin-guided antibiotic therapy for lower respiratory tract infections" @default.
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